Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent

Abstract

Background and Purpose While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent (GBCA) administration in adults, a retrospective series of pediatric patients has not previously been reported. We investigated the relationship between the number of prior GBCA doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that, despite differences in pediatric physiology and the smaller GBCA doses pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose dependent increasing T1 signal in the dentate nucleus. Materials and methods We included children with multiple GBCA administrations at our institution. A blinded-reader placed regions of interest (ROIs) within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons was also performed. Dentate to cerebellar white matter (DN/C) and dentate to pons (DN/P) ratios were compared to the number of GBCA administrations. Results Over 20 years at our institution, 280 patients received at least 5 GBCA doses with one patient receiving 38 doses. Sixteen patients met inclusion/exclusion criteria for ROI analysis. Blinded-reader DN/C ratios were significantly associated with GBCA doses (rs=0.77, p=0.001). DN/P and DN/C ratios based on automated ROI placement were also significantly correlated with GBCA doses (t=4.98, p<0.0001 and t=2.73, p<0.02 respectively). Conclusion In pediatric patients, the number of prior GBCA doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance including the use in pediatric patients of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most importantly, a patient should not be deprived of a well-indicated contrasted MR exam.

T1 Signal Measurements in Pediatric Brain: Findings after Multiple Exposures to Gadobenate Dimeglumine for Imaging of Nonneurologic Disease

“…(GBCAs). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Many of these reports have focused on apparent differences between macrocyclic and open-chain "linear" GBCAs, [4][5][6][7][8][9][10][11][12][13] invariably associating progressive T1 hyperintensity with multiple exposures to linear GBCAs and concluding that observed T1 signal reflects the lower stability of these agents and thus a greater propensity for gadolinium (Gd) release and, subsequently, deposition in the brain. Among the more recent reports are several that describe retrospective assessments in pediatric patients.…”

Magnetic resonance imaging to diagnose leptomeningeal spread of medulloblastoma in children: Decreasing diagnostic uncertainty, moving in new directions

“…Two recent developments have generated interest in decreasing the use of intravenous gadolinium‐based contrast materials. The first was the concern that has arisen regarding gadolinium deposition within and outside of the brain and potentially related toxicity in children undergoing multiple surveillance MRI examinations utilizing gadolinium . Brain and bone tissue deposition of gadolinium has been detected even in patients with normal renal function, although the clinical consequences (if any) are currently unclear .…”

“…The first was the concern that has arisen regarding gadolinium deposition within and outside of the brain and potentially related toxicity in children undergoing multiple surveillance MRI examinations utilizing gadolinium. 8 Brain and bone tissue deposition of gadolinium has been detected even in patients with normal renal function, although the clinical consequences (if any) are currently unclear. 9 Therefore, at our institution, we In the attempt to minimize gadolinium exposure and to increase the sensitivity to detect nonenhancing leptomeningeal spinal disease, newer noncontrast MRI techniques have been suggested.…”

The Effects of Gadolinium-Based Contrast Agents on the Cerebellum: from Basic Research to Neurological Practice and from Pregnancy to Adulthood

“…1 [15][16][17][18][19], showed a significant decrease in the time spent on the rotarod on day 3 in both GBCA-treated groups (gadoterate meglumine-treated group, p < 0.001 and gadodiamide-treated group, p < 0.001, by ANOVA followed by Bonferroni test) compared with that in the control group. ***p < 0.001…”

“…After (a) repeated reports of signal intensity (SI) increase in the dentate nuclei and basal ganglia on brain T1-weighted images of pediatric patients who underwent several contrastenhanced MRI scans with administration of linear products [16][17][18][19] and (b) a study with no SI after gadobenate administration [20], an autoptic study of three children has confirmed the deposition of gadolinium in the dentate nucleus, globus pallidus, and at a smaller concentration in the thalamus and pons, after more than 3 administrations of gadodiamide, a linear GBCA [21]. Pathological changes were also observed in the dentate nuclei (gliosis, axonal spheroids).…”